The expression of the multidrug resistance-associated protein (MRP), a new glycoprotein involved in drug resistance, Tvas investigated in peripheral blood cells from healthy volunteers as well as in >140 tumor samples from patients with hematological malignancies by a quantitative RNase protection assay and by immunohistochemistry. MRP appeared to be ubiquitously expressed at low levels in all nonmalignant hemopoietic cell types, reflecting its basal constitutive expression. In chronic lymphocytic leukemia (CLL), a high percentage of patients (20/32: 63%) had relatively high (hyper) expression levels of the MRF gene (25 U or more). Furthermore, hyperexpression of the MRP gene was demonstrated in 4/10 (40%) untreated patients with prolymphocytic leukemia (PLL) and in 4/43 (9%) patients (irrespective of prior chemotherapy) with acute myelocytic leukemia (AML). Although a significant number of AML patients (9/43: 21%) showed elevated mRNA levels (10-25 U) of the MRP gene, the majority showed low (1-10 U) but detectable MRP expression. Predominantly low MRP mRNA expression levels were detected in acute lymphoid leukemia (ALL), chronic myelocytic leukemia (CML), hairy cell leukemia (HCL) non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). We conclude that relatively high expression of MRP is occasionally observed in AML and at high frequency in GILL and PLL. MRP hyperexpression in leukemia is irrespective of prior chemotherapy and not correlated with clinical stage of the disease and is probably due to transcriptional activation or increased mRNA stability.